Liquid biopsy: from concept to clinical application

The diagnosis and treatment of cancer presents a physical and mental burden to the patient, often involving diagnostic biopsies and surgeries or chemotherapeutic approaches with severe side-effects. Advances which enable early detection of cancer and close monitoring of the disease course without invasive procedures, and which can underpin a tailored approach to treatment, can therefore make a big difference to the quality of life of patients. Liquid biopsies can be used to access tumor cells and tumor DNA circulating in the blood. Monitoring these species can provide a minimally invasive and repeatable means to detect cancer, or gain information about its response to treatment.


Exosomes
Shaikh et al. investigated the expression levels of a specific gene panel in exosomes isolated from patients with oral cancer to lymph nodes metastasis along with an integrated computational screening 14 .Their significant gene signature identification demonstrated increased serum exosome efficacy in early detection and was clinically associated with intracellular communication in the formation of the premetastatic niche.
In conclusion, liquid biopsy analyses can be used to gain new insights into the biology of metastasis, its prediction and/or prevention, to be a companion diagnostic to improve therapy stratification, and to gain insights into therapy-induced cancer cell selection.Within these contexts, intra-patient tumor heterogeneity may be an important mechanism to investigate for total eradication of all tumor clones, including but also extending CTC subsets, by targeted therapies 15 .In addition, the synergy of multiple circulating biomarkers can reveal the molecular specifics of cancer 16 .
Researchers and clinicians have been aware for many years of the potential value of liquid biopsies as useful tools to complement current therapies non-invasively and in real-time in the patients 17,18 .Liquid biopsy has also been implemented in clinical trials to measure biomarkers indicative of treatment response 19 and prognosis [20][21][22] , meanwhile observational studies demonstrated the clinical utility of liquid biopsy to predict therapeutic response before it is clinically apparent [23][24][25] and to better understand the biology of tumors 26 .Personalized mutation tracking using custom-made bespoke assays have also been designed for non-metastatic patients to allow for a more accurate screening for disease recurrence while patients are potentially curable 27 .
More interventional clinical trials are urgently needed to widely implement liquid biopsy in clinical practice.Policymakers and business leaders must participate in these clinical trials and discussions in order to make national and international decisions.Of particular significance, the multi-center standardization of preanalytical and analytical methods is imperative before liquid biopsy can be consistently used in clinical settings.Big consortia such as the European Liquid Biopsy Society (ELBS; www.elbs.eu) in the EU, or the BLOODPAC in the U.S.A. continue to lead significant programs to complete this mission and develop and validate a wide range of standard operating procedures.There is also a clinically unmet need for more studies of liquid biopsy approaches to diagnose cancer before it is clinically evident, particularly for those types of cancer in which there is no clinical screening testing available 28 .
Multidisciplinary collaboration between academia, the biotechnology and pharmaceutical industries, and other stakeholders will be crucial in moving the field forward.We anticipate that precision medicine approaches that identify high-risk patient populations and predict specific therapeutic benefit for patients will ultimately succeed in gaining clinical traction as the field moves beyond simply enumerating the presence of minimal residual disease to incorporating liquid biopsy in well-designed clinical trials in cancer.
Finally, this collection of articles highlights the diversity of liquid biopsy approaches and the many strengths afforded by each strategy.Many challenges still remain to make liquid biopsy a reality in the clinic.We hope it will inspire researchers to continue innovating the applications of liquid biopsy and making important discoveries as we work together towards the goal of translating liquid biopsy to the clinic to improve outcomes for cancer patients.